Sulfuric Acid → 4-(3-Picolinoyltetrahydrofuran-3-yl)benzonitrile
Reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2(C#N)[CH2:25][CH2:24][O:23][CH2:22]2)=[CH:17][CH:16]=1)#[N:14].OS(O)(=O)=O.C1C[O:36][CH2:35]C1>>[N:3]1[CH:4]=[CH:5][CH:6]=[C:7]([C:35]([CH:22]2[CH:21]([C:18]3[CH:17]=[CH:16][C:15]([C:13]#[N:14])=[CH:20][CH:19]=3)[CH2:25][CH2:24][O:23]2)=[O:36])[CH:2]=1Participants
Procedure
To a solution of 2-bromopyridine (0.412 g, 2.6 mmol) in dry THF was added n-BuLi (1.05 mL, 2.5 M solution in n-hexane) at −78° C. After stirring for 15 minutes, the solution of Example 79A (0.345 g, 1.74 mmol) in THF (2 mL) was added. The mixture was stirred at −78° C. for 15 minutes, then 5 mL of 1 M H2SO4 solution was added slowly. The mixture was heated at about 50° C.-60° C. for 30 minutes. The aqueous phase was separated and extracted with EtOAc (3×50 mL). The combined organic phases was washed with water (2×50 mL) and brine (50 mL) respectively, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography (petroleum ether:EtOAc=3:1) to provide the title compound (65 mg, 13.4%). LC-MS: m/z 279 (M+H).
Workup
- stirringThe mixture was stirred at −78° C. for 15 minutes
- temperatureThe mixture was heated at about 50° C.-60° C. for 30 minutes
- customThe aqueous phase was separated
- extractionextracted with EtOAc (3×50 mL)
- washThe combined organic phases was washed with water (2×50 mL) and brine (50 mL) respectively
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by silica gel column chromatography (petroleum ether:EtOAc=3:1)
Sources & evidence
- ORD record
- ord-1c1cb8e62ab5478ebdab3ccaf55b4a0b
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772500B2
Reaction notes
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